Association between decreased CXCL12 and CCL25 expression and increased apoptosis in lymphoid tissues of cynomolgus macaques during SIV infection

Abstract

Chemokines likely play multiple roles in HIV-1 and SIV pathogenesis. To examine potential associations between chemokine expression levels and apoptosis of cells in lymphoid tissues during SIV infection, we measured chemokine and cytokine mRNA levels in multiple lymphoid tissues compartments from uninfected and SIV-infected cynomolgus macaques (Macaca fascicularis). Real-time RT-PCR was used to measure host mRNA levels in macaque lymphoid tissues. Proliferating or apoptotic cells were identified in lymphoid tissues by immunohistochemistry. We found that CXCL12 and CCL25 mRNAs in SIV-infected lymphoid tissues were decreased and their levels were negatively correlated with the numbers of proliferating and apoptotic cells. In vitro analyses revealed that CXCL12 and CCL25 were capable of reducing apoptosis induced by SIV infection. These findings suggest that increased apoptosis in lymphoid tissues due to reduced levels of anti-apoptotic chemokines might be a mechanism that contributes to loss of immune function following pathogenic SIV infection.